P1188: PERSONALIZED TREATMENT ACCORDING TO BIOLOGICAL PROFILE IMPROVES OUTCOME OF NEWLY DIAGNOSED PATIENTS AFFECTED BY DIFFUSE LARGE B-CELL LYMPHOMA: A REAL-LIFE EXPERIENCE
Authors: A. Guidetti, R. Pasquale, A. Dodero, A. Chiappella, L. Devizzi, L. Farina, C. Rusconi, M. Pennisi, P. Corradini
Journal: HemaSphere (2022)

Background: Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous disease characterized by biological and clinical aspects conditioning different prognosis. Chemo-immunotherapy treatment with R-CHOP proved to be less effective in patients with double hit (DH)/triple hit (TH) or double expressor (DE) DLBCL who require more intensive regimens Aims: To investigate survival outcomes of DLBCL patients treated according to biological profile in the real-life clinical practice at Istituto Nazionale dei Tumori in Milano. Primary objective was to verify whether personalized treatment could overcome well known differences in Progression Free Survival (PFS) observed between DE, DH/TH and non DE/DH/TH patients when they are uniformly treated with R-CHOP Methods: We retrospectively collected clinical and survival data of all newly diagnosed DLBCL patients referred at our Hematology Division from January 2013 to August 2021. All DLBCL patients are evaluated for BCL2, BCL6 and MYC expression in immunohistochemistry and gene rearrangements by fluorescent in situ hybridization, and they are assigned to treatment based on the biologic profile: non DE/DH/TH patients receive 6 cycles R-CHOP-21 + 2R, DE patients receive 6 cycles R-DA-EPOCH and DH/TH receive R-CODOX-M/R-IVAC. Central Nervous System (CNS) prophylaxis with lumbar puncture and/or intravenous high dose methotrexate is reserved for DE or DH patients and for those with CNS-IPI 3-5 Results: Since 2013, 243 patients affected by DLBCL at diagnosis were consecutively treated according to biological risk: 139 non DE/DH/TH patients received R-CHOP, 80 DE patients received R-DA-EPOCH and 24 high risk patients received R-CODOX-M/R-IVAC (n= 13 DH/TH patients and n=11 DE patients with CNS IPI 3-5). Median age was 62 years (range, 21-86), 178 patients (73%) presented in stage 3-4 and 97 patients (40%) had an IPI score of 3-5. The three groups were not significantly different in terms of clinical characteristics, except for median age, which was higher in the R-CHOP group (66 years vs. 58 and 57 years in R-DA-EPOCH and R-CODOX-M/R-IVAC groups, respectively). Despite the toxicity expected with an intensified therapy, 95% of patients completed the treatment and no toxic deaths were registered. Febrile neutropenia was observed in 3%, 15% and 29% of patients in RCHOP, RDAEPOCH and RCODOX-M/R-IVAC, respectively. At a median follow-up of 42 months (range, 2-106 months), the estimated 3 years PFS and OS for the entire population were 80% and 89%, respectively. Patients with low IPI, limited stage and germinal center B cell of origin had significant better PFS as compared to the rest. Three years PFS and OS according to biological entity and relative treatment group were not significantly different, being 84%, 77% and 66%, (p=ns) and 93%, 85% and 74%, (p=ns) in non DE/DH/TH, DE and high risk patients, respectively. Similar PFS between non DE/DH/TH, DE and high risk patients were observed also in the subgroup of patients with IPI3-5 with PFS of 77%, 65% and 57%, respectively (p=ns). CNS prophylaxis was administered to 177 patients (73%) and 9 cases of CNS recurrence (4%) were observed Summary/Conclusion: In this study, we describe the feasibility of a personalized treatment according to biological risk in a real-life setting. This approach seems to overcome the poor outcome of DLBCL patients at high risk of relapse and ameliorate the prognosis of the overall DLBCL population. Biological characteristics should be carefully considered at diagnosis in order to give patients a personalized program and improve their outcome